Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2′-ligands

A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.

Graphical abstractA series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.Figure optionsDownload full-size imageDownload as PowerPoint slide